P1080: COMPARISON OF NIVOLUMAB 40 MG EFFICACY VERSUS 3 MG/KG IN PATIENTS WITH RELAPSED AND REFRACTORY CLASSIC HODGKIN LYMPHOMA
Authors: L. Fedorova, K. Lepik, N. Mikhailova, E. Kondakova, Y. Komarova, M. Popova, P. Kotselyabina, E. Borzenkova, V. Baykov, I. Moiseev, A. Kulagin
Journal: HemaSphere (2022)

Background: Nivolumab 3 mg/kg was shown to be effective in patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL). However, previously obtained data on pharmacokinetics, as well as financial toxicity of therapy, raised the issue of studying necessity of efficacy of reduced doses of PD-1 inhibitors. Efficacy of nivolumab 40 mg has previously been demonstrated in patients with r/r cHL in a prospective phase 2 study (Lepik KV et al., 2020). Continued accumulation of experience in the use of low-dose PD-1 inhibitors in patients with r/r cHL is required to support previous data. Aims: To compare the efficacy of nivolumab (Nivo) 40 mg therapy with 3 mg/kg for patients with r/r cHL. Methods: The Nivo40 trial (NCT03343665) expanded prospective cohort of patients (group 1, n=50) treated with Nivo 40 mg was compared with the retrospective group 2 (n=116) of patients treated with Nivo 3 mg/kg. Patients characteristics are demonstrated in the Table 1. The response was evaluated every 3 months by PET-CT using LYRIC criteria. Adverse events (AE) were analyzed by NCI CTCAE 4.0.3. Overall response rate, progression-free survival (PFS) and overall survival (OS) were compared between group 1 and 2. During the survival analysis the PFS was censored by the time of additional therapy initiation. - Variable Nivo 40 mgN=50 Nivo 3 mg/kgN=116 p Median age, years (range) 36 (20-54) 38 (14-65) 0.129 Male/female, n (%) 17/33 (34/66) 56/60 (48/52) 0.089 Primary chemoresistance, n (%) 38 (76) 74 (64) 0.124 Early relapse, n (%) 7 (14) 14 (12) 0.731 Prior autologous stem cell transplantation, n (%) 17 (34) 44 (38) 0.630 Prior brentuximab vedotin, n (%) 18 (36) 62 (53) 0.039 Therapy lines before Nivo therapy, n (range) 4 (1-8) 5 (2-10) 0.011 B symptoms at Nivo therapy initiation, n (%) 26 (52) 71 (61) 0.269 Disease stage at Nivo therapy initiation, n (%) 2 8 (16) 11 (9) 0.294 3 5 (10) 7 (6) 4 37 (74) 97 (84) Progression at Nivo therapy initiation, n (%) 46 (92) 92 (79) 0.272 ECOG status at Nivo therapy initiation, n (%) 0-1 31 (62) 70 (60) 0.758 2 14 (28) 29 (25) 3 4 (8) 14 (12) 4 1 (2) 2 (2) Results: Median follow up was 44 (11-55) months in group 1 and 60 (6-70) months in group 2. Median Nivo cycles was 19 (2-49) and 20 (1-32) respectively. The best response to Nivo therapy was detected at 6 (2-24) and 6 (1-27) cycles respectively. Overall response rate was 66% in group 1 and 67% in group 2. The structure of response in group 1 was: complete response (CR) in 38% of patients, partial response (PR) in 28%, stable disease (SD) in 6%, indeterminate response (IR) in 22% and progressive disease (PD) in 6%; in group 2: CR in 34%, PR in 33%, SD in 5%, IR in 20% and PD in 8%. Median OS was not achieved in both groups, 3-year OS was 97,8% and 96,5% respectively (p=0.356). Median PFS was 21,9 months (95%CI: 16,75-27,05) in group 1 and 18,8 months (95%CI: 13,44-24,16) in group 2, 3-year PFS was 25,6% and 27% respectively (p=0.356). Additional therapy after Nivo monotherapy was started in 78% of patients after Nivo 40 mg and in 84% after Nivo 3 mg/kg. Allogeneic stem cell transplantation after Nivo therapy was performed in 5 (10%) patients in group 1 and in 26 (22%) patients in group 2. Any grade adverse events were detected in 66% of patients in group 1 and in 79% in group 2 (p=0.068), 3-4 grade AE were detected in 10% and 19% respectively (p=0.151). Summary/Conclusion: Nivolumab 40 mg therapy is comparable to the standard dose of 3 mg/kg in terms of overall response rate as well as survival in patients with r/r cHL. However, a direct comparison of different doses of nivolumab in a prospective study is required.